Murine experimental allergic orchitis (EAO) has been induced with mouse testis homogenate (TH) or rat Sertoli cell plasma membrane (RSCPM), using Bordetella pertussis extract (BPE) as adjuvant. Before EAO onset, transient mouse IgG deposit in or adjacent to Setoli cells and degeneration of Setoli cells (early testicular changes) were observed. Both major histocompatibility (MHC) and non-MHC genes were involved in genetic control of murine EAO. Orchitis and vasitis may be induced by different antigens, and are under separate genetic control. Experiments, based on these new findings, are designed to clarify the pathogenesis of murine EAO as model of organ-specific auto-immune disease, as a cause of male infertility, and as a mew approach to study Sertoli cell biology. To characterize early testicular changes, testicular IgG will be localized by immunoperoxidase technique, and its antibody specificity identified after being eluted with acid pH. Mechanisms leading to these changes will be examined by studing antigen and adjuvant requirements in their induction; and by testing the hypothesis that these changes are due to anaphylactic antibody response to Sertoli cell surface antigens and BPE-induced hypersensitivity to vasoactive amines. The status of the blood-testis (BT) barrier during early testicular changes will be investigated by permeation of lanthanum, peroxidase and fluorescent dextran. Any association of testicular IgG and defective BT barrier with the spermatogenic cycle will be determined. Whether the early testicular changes are causally related to EAO will be investigated by their correlation in the same animal, and between EAO responsive and nonresponsive mouse strains. Aspermatogenic molecules will be isolated from RSCPM; and EAO induced by RSCPM defined with respect to nature and distribution of pathology, immunohistochemical changes and immune responses to RSCPM. Passive transfer of EAO with immune reactants to RSCPM may suggest whether Sertoli cell autoantigens are located outside the BT barrier. Cellular changes and secretion of plasminogen activators by Sertoli cells upon interaction with anti-Sertoli cell antibody will be studied in vitro. To further explore pathogenesis of murine EAO, location of immune response genes and nature of the genetic control of EAO, of disease distribution, of immune responses to testicular antigens, and of susceptibility of the testis to EAO induction will be analyzed in inbred, congenic and mutant mice; in F1 and backcross progeny of EAO responsive and noresponsive parents immunized with TH, RSCPM and RSCPM antigens.